I. Mahadevan et M. Rasmussen, AMBIDENT HETEROCYCLIC REACTIVITY - THE ALKYLATION OF PYRROLOPYRIDINES(AZAINDOLES, DIAZAINDENES), Tetrahedron, 49(33), 1993, pp. 7337-7352
7-Methyl-6-azaindole, 7-acetamido-4-azaindole, the substituted 4-amino
-, 2-methyl- and 6-methyl-7-azaindole, and the parent 4-, 5-, 6-, and
7-azaindole systems (as anions in dimethylformamide) were alkylated wi
th a variety of primary alkylating agents. The relative importance of
charge, product development, and steric approach control in determinin
g the alkylation pattern (pyrrole versus pyridine ring alkylation) are
discussed within a framework of variable S(N)2 transition state struc
tures. Frontier orbital factors appear to be relatively insignificant.
The charge distribution, orbitals and energetics of these heterocycli
c systems were modelled by ab initio molecular orbital calculations (S
TO-3G level). Specific association, involving hydrogen bonding between
adjacent groups and the alkylating agent, is important in determining
the alkylation pattern in some cases.